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Septic ArthritisWhen elevated, these markers may be used to moni- pathogen, underlying medical conditions, or exposurestor therapeutic response. Because pathogenesis may (Table 4 7,18,20,31-34). Clinical presentations can be broadlybe hematogenous, blood cultures are positive in 25 to grouped into three categories: nongonococcal, gonococ-50 percent of patients with septic arthritis.1,9,20 cal, and other (e.g., Lyme disease, mycobacterial, fungal).SYNOVIAL FLUID ANALYSIS NONGONOCOCCAL ARTHRITISBecause the clinical presentation of septic arthritis may Septic arthritis is caused by nongonococcal patho-overlap with other causes of acute arthritis (Table 2 6,16), gens in more than 80 percent of patients.2 Nongono-arthrocentesis is needed to identify the causative coccal arthritis often affects older persons, is acute ininfectious agent. Synovial fluid should be evaluated nature, and is monoarticular in more than 80 percentat the bedside and then sent for WBC count with dif- of patients.12 Synovial fluid cultures are positive in moreferential, crystal analysis, Gram stain, and culture21-23 than 90 percent of patients with nongonococcal arthri-(Table 319-21,24-26). In synovial fluid, a WBC count of more tis, as opposed to blood cultures, which are positive inthan 50,000 per mm3 (50 × 109 per L) and a polymor- only 50 percent of patients.12,30phonuclear cell count greater than 90 percent have been Gram-positive staphylococci and streptococci are thedirectly correlated with infectious arthritis, although causative agents in the majority of bacterial arthritisthis overlaps with crystalline disease.1,6 Lower synovial cases in which an organism is identified,3 and are associ-fluid WBC counts may occur in persons with dissemi- ated with drug abuse, cellulitis, abscesses, endocarditis,nated gonococcal disease, peripheral leukopenia, or joint and chronic osteomyelitis.18 Staphylococcus aureus is thereplacement.6,19,22 Septic arthritis can coexist with crystal organism most commonly found in patients with septicarthropathy; therefore, the presence of crystals does not arthritis in the United States and other developed coun-preclude a diagnosis of septic arthritis.27 tries,30,35 and Streptococcus species is the next most com- Measuring synovial fluid glucose or protein is not use- mon.30,36 The presence of methicillin-resistant S. aureusful because results are neither sensitive nor specific for (MRSA) is an emerging clinical problem. Although dataseptic arthritis.6 Polymerase chain reaction (PCR) testing are mostly limited to case reports, the incidence of MRSAmay help isolate less common organisms, such as Borrelia ranges between 5 and 25 percent of bacterial arthritisspecies,24,25 and should be ordered if there is a high level cases, and tends to affect older persons, involve the shoul-of clinical suspicion. The sensitivities of synovial fluid, der, and the health care–associated MRSA strain.37,38Gram stain, and culture vary by pathogenic organism. Gram-negative bacilli represent approximately 14 to 19 percent of septic arthritis cases12,18 and are associ-IMAGING ated with invasive urinary tract infections, intravenousThere are no data on imaging studies that are pathogno- drug use, older age, compromised immune system,monic for acute septic arthritis. Plain films establish a and skin infections.18 The two most common gram-baseline and may detect fractures, chondrocalcinosis, or negative organisms detected in adults are Pseudomonasinflammatory arthritis. Ultrasonography is more sensi- aeruginosa and Escherichia coli.10,12,17,18 Historically, Hae-tive for detecting effusions, particularly in difficult-to- mophilus influenzae infection has occurred more oftenexamine joints, such as the hip.28 Magnetic resonance in children,2,39 although this may be tempered by wide-imaging findings that suggest an acute intraarticular spread H. influenzae type b vaccination.40infection include the combination of bone erosions with GONOCOCCAL ARTHRITISmarrow edema.29 Imaging may allow guided arthrocen-tesis, particularly in difficult-to-examine joints (e.g., Patients with disseminated Neisseria gonorrhoeae infec-hip, sacroiliac, costochondral). tion are usually young, healthy, and sexually active.30 Disseminated gonococcal infection may have variousOrganisms clinical musculoskeletal presentations, with or withoutAlmost any microorganism may be pathogenic in sep- associated dermatitis. Patients typically display a migra-tic arthritis. Bacterial causes of septic arthritis include tory pattern of arthralgias, tenosynovial inflammation,staphylococci (40 percent), streptococci (28 percent), or nonerosive arthritis.6,23,30 Blood cultures are seldomgram-negative bacilli (19 percent), mycobacteria (8 per- positive, and synovial fluid cultures are variable, with acent), gram-negative cocci (3 percent), gram-positive positive result in only 25 to 70 percent of patients withbacilli (1 percent), and anaerobes (1 percent).30 There are gonococcal arthritis.19,23 When a disseminated gonococ-various characteristic presentations depending on the cal infection is suspected, cultures should be taken fromSeptember 15, 2011 ◆ Volume 84, Number 6 www.aafp.org/afp American Family Physician 655

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Septic ArthritisCulture PCR test Crystals Borrelia burgdorferi infection initially causes viral-likeNegative Negative Negative migratory arthralgias of Lyme disease. Late disease isNegative Negative Negative characterized by an intermittent oligoarthritis that usu-Negative Negative Positive ally involves the knee or other large joints.44 The diagnosis of Lyme arthritis can be made with a two-step serologic testing process involving enzyme-linked immunosor-Negative Negative Negative bent assay, followed by confirmation with a Western blot or immunoblot test.45 B. burgdorferi cannot be culturedNegative Positive (85 percent) Negative from synovial fluid46 ; however, PCR testing is positive in 85 percent of patients with Lyme arthritis, making it aPositive (25 to 70 percent) Positive ( 75 percent) Negative confirmatory test.47 It should be noted that PCR testing cannot distinguish live from dead organisms.46Positive ( 90 percent) — Negative* Management Empiric intravenous antibiotic treatment of septic arthritis should be based on the organism found in the Gram stain of the synovial fluid, or on the suspicion of a pathogen from the patient’s clinical presentation (Table 4 7,18,20,31-34). Treatment options include vancomy- cin for gram-positive cocci, ceftriaxone (Rocephin) for gram-negative cocci, and ceftazidime (Fortaz) for gram- negative rods (Table 5 32). If the Gram stain is negativepotentially infected mucosal sites (e.g., urethra, rectum, but there is suspicion of bacterial arthritis, vancomy-pharynx, cervix).30,41 PCR testing has a sensitivity of cin plus either ceftazidime or an aminoglycoside is76 percent and a specificity of 96 percent for N. gonor- appropriate.32 Adjustments to the administration routerhoeae, and may be useful in patients with culture- and the duration of treatment should be based on thenegative disease if the clinical scenario is unclear or sim- clinical response and microbiology results. The Sanfordilar to a reactive arthritis.26 Guide (http://www.sanfordguide.com; subscription required) is a resource for the management of infectiousOTHER INFECTIONS syndromes. It includes dosing options for patients withFungal arthritis usually has an insidious onset and indo- renal insufficiency and drug allergies, and lists commonlent course.42,43 Pathogen-specific clinical scenarios are drug interactions.presented in Table 4.7,18,20,31-34 Synovial fluidcultures or biopsy can confirm the diagnosis. Mycobacterial infectious arthritis is also Table 5. Empiric Antibiotic Therapy for Suspectedindolent, which can cause a considerable Bacterial Arthritisdelay in diagnosis, although joint damagedoes not occur as rapidly as it does in bac- Gram stain result Antibioticterial infections.31 Articular Mycobacteriumtuberculosis infection typically affects the Gram-positive cocci Vancomycinhip or knee; is usually caused by reactiva- Gram-negative cocci Ceftriaxone (Rocephin)tion from past dissemination; and may occur Gram-negative rods Ceftazidime (Fortaz), cefepime (Maxipime),without other manifestations of active tuber- piperacillin/tazobactam (Zosyn), or carbapenemsculosis. 31,42 Synovial fluid culture is positive If patient is allergic to penicillin or cephalosporins: aztreonam (Azactam) or fluoroquinolonesin 80 percent of patients with M. tuberculosis Negative Gram stain Vancomycin plus either ceftazidime or aninfection. Acid-fast smears are not help- 34 aminoglycosideful and are often negative.31 Histology is notspecific because it may mimic other granu- NOTE: A general guide for antibiotic selection should be used to help determine dos-lomatous diseases, although synovial biopsy ages for individual patients.will be positive for M. tuberculosis in about Information from reference 32.95 percent of cases.34September 15, 2011 ◆ Volume 84, Number 6 www.aafp.org/afp American Family Physician 657

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Septic Arthritis Table 6. Phases of Prosthetic Joint Infections Timing after Infection joint replacement Clinical presentation Mode of infection Common pathogens Early Less than three Erythema, warmth, fever, chills, During implantation Staphylococcus aureus, months joint pain, effusion, excessive gram-negative bacilli perioperative drainage Delayed Three to 24 months Persistent pain and/or aseptic During implantation Coagulase-negative staphylococci, loosening Propionibacterium acnes Late More than Sudden-onset joint pain; fever Hematogenous Same as native joints 24 months and leukocytosis less likely Information from references 19, and 63 through 65. The duration of therapy in patients with nongono- baseline joint function.9 In contrast, adults with pneu-coccal septic arthritis is typically three to four weeks. mococcal septic arthritis who survive infection (theTherapy for disseminated gonococcal infection involves mortality rate is approximately 20 percent) will return toa third-generation cephalosporin, such as ceftriaxone, 95 percent of their baseline joint function after complet-for 24 to 48 hours after improvement begins, followed ing antimicrobial therapy.3 Morbidity (e.g., amputation,by oral therapy.41 The clinical response should be rapid, arthrodesis, prosthetic surgery, severe functional dete-with symptoms improving within 24 to 48 hours. Treat- rioration) occurs in one-third of patients with bacterialment then may be switched to oral cefixime (Suprax), arthritis, usually affecting older patients, those with pre-or ciprofloxacin (Cipro) if quinolone resistance is not a existing joint disease, and those with synthetic intraar-concern, for at least one week.41 Treatment of chlamydia ticular material.52also should be considered in the absence of appropri-ate testing.41 Treatment of fungal arthritis is species- Special Considerationsdependent, but usually includes an oral azole or paren- Prosthetic joint infections occur in 0.86 to 1.1 percentteral amphotericin B.42,43 Lyme arthritis responds well to of knee arthroplasties53,54 and in 0.3 to 1.7 percent of hipparenteral ceftriaxone or oral doxycycline.47 arthroplasties.53,55 These infections may result in failure In addition to antibiotic therapy, evacuation of puru- of the joint replacement. In prosthetic joint infections,lent material is necessary. Guidelines from 2006 do bacterial adherence to prosthetic surfaces forms bio-not distinguish between arthrocentesis and surgical films, which can lead to increased resistance to the host’smethods.48 Repeated daily joint aspirations are success- immune system and to antimicrobials.56-58ful during the first five days of treatment.49 With each Prosthetic joint infections are usually caused byaspirate, synovial fluid WBC count, polymorphonuclear gram-positive cocci, including coagulase-negativecell count, Gram stain, and culture should be evaluated staphylococci and S. aureus.53,54 Other organisms, suchto ensure clinical response. Open or arthroscopic tech- as gram-negative bacilli53,59 and mycobacteria,60 haveniques can be used to surgically drain the infected joint. also been implicated. Polymicrobial infections afterArthroscopic drainage is associated with rapid recovery hip and knee arthroplasties have been reported in up toand low morbidity.50 Direct visualization of the joint tis- 20 percent of patients.61 Risk factors for the developmentsue facilitates the lysis of adhesions, drainage of purulent of prosthetic joint infections include previous fracture,pockets, and debridement of necrotic material. seropositive rheumatoid arthritis, high body mass index, revision arthroplasty, and surgical site infections.59,61,62Prognosis Table 6 19,63-65 lists the three categories of prosthetic jointBefore antibiotics were available, two-thirds of patients infections with typical pathogenesis, timing, clinicaldied from septic arthritis.51 Current mortality rates of presentation, and mode of infection.bacterial arthritis range from 10 to 20 percent, depend- A key distinction in the diagnostic workup of patientsing on the presence of comorbid conditions, such as with a prosthetic joint infection is that the intraarticularolder age, coexisting renal or cardiac disease, and con- WBC cutoff values for infection may be as low as 1,100current immunosuppression.3,9,52 Factors associated with per mm3 (1.10 × 109 per L), with a neutrophil differen-death include age 65 years or older, and infection in the tial of greater than 64 percent.66 This low WBC count,shoulder, elbow, or at multiple sites.52 combined with occasionally more indolent clinical pre- After completing antimicrobial therapy, patients with sentations, can make diagnosis problematic. DiagnosticS. aureus septic arthritis regain 46 to 50 percent of their imaging modalities include fluorodeoxyglucose positron658 American Family Physician www.aafp.org/afp Volume 84, Number 6 ◆ September 15, 2011